Genetic Variant C1QTNF4:p.Asp159Asn (chr11-47590336-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031909.3(C1QTNF4):c.475G>A(p.Asp159Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000252 in 1,309,714 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

C1QTNF4
NM_031909.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Publications

0 publications found

Variant links:

Genes affected

C1QTNF4 (HGNC:14346): (C1q and TNF related 4) Predicted to enable cytokine activity. Involved in positive regulation of cytokine production and positive regulation of signal transduction. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

C1QTNF4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031909.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF4	NM_031909.3	MANE Select	c.475G>A	p.Asp159Asn	missense	Exon 2 of 2	NP_114115.2	Q9BXJ3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C1QTNF4	ENST00000302514.4	TSL:1 MANE Select	c.475G>A	p.Asp159Asn	missense	Exon 2 of 2	ENSP00000302274.3	Q9BXJ3
C1QTNF4	ENST00000862513.1		c.475G>A	p.Asp159Asn	missense	Exon 3 of 3	ENSP00000532572.1
C1QTNF4	ENST00000954826.1		c.475G>A	p.Asp159Asn	missense	Exon 2 of 2	ENSP00000624885.1

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

148458

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000299

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1161256

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

559858

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22122

American (AMR)

AF:

0.00

AC:

AN:

8398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14884

East Asian (EAS)

AF:

0.00

AC:

AN:

24034

South Asian (SAS)

AF:

0.00

AC:

AN:

48456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3194

European-Non Finnish (NFE)

AF:

0.0000321

AC:

AN:

965802

Other (OTH)

AF:

0.00

AC:

AN:

46472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000135

AC:

AN:

148458

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40964

American (AMR)

AF:

0.00

AC:

AN:

14914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3426

East Asian (EAS)

AF:

0.00

AC:

AN:

5058

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000299

AC:

AN:

66884

Other (OTH)

AF:

0.00

AC:

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.96

M_CAP

Pathogenic

0.47

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.3

PhyloP100

5.1

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.4

REVEL

Benign

0.19

Sift

Uncertain

0.010

Sift4G

Uncertain

0.027

Polyphen

1.0

Vest4

0.51

MutPred

0.57

Loss of sheet (P = 0.0457)

MVP

0.57

ClinPred

0.95

GERP RS

2.9

PromoterAI

-0.096

Neutral

(source)

Varity_R

0.31

gMVP

0.38

Mutation Taster

=58/42

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over